Flexible valve for administering constant flow rates of medicine from a nebulizer

ABSTRACT

A nebulizer is improved by placing a flexible valve in the ambient air inlet tube. Inhalation suction and Venturi effect shut down the flexible valve in proportion to the strength of the inhalation. Thus, the same output flow rate is obtained even with variable strength inhalations. Medications can be properly administered by controlled inhalation flow rates.

CROSS REFERENCED PATENTS

U.S. Pat. No. 4,106,503 (1978) to Rosenthal et al. is incorporatedherein by reference. This application is a divisional of U.S.application Ser. No. 08/110,549, filed Aug. 23, 1993, issued as U.S.Pat. No. 5,655,520 on Aug. 12, 1997.

FIELD OF INVENTION

The present invention relates to fixed rate flow valves particularlyuseful in administering constant rates of medicine via inhalation.

BACKGROUND OF THE INVENTION

A nebulizer is commonly used in respiratory therapy and in medicalresearch to dispense an aerosol. Atomization of the aerosol occurs aspressurized air is fed into the bottom of the nebulizer bowl. Thepatient inhales through an outlet orifice at the top of the nebulizer.This forces the aerosol into the respiratory system. It is customary toregulate the time interval of the pressurized air flow with each breath.Short timed bursts of pressurized air are used to atomize the liquid inthe nebulizer. The dosimeter shuts off the air flow at predeterminedtimes after each inhalation. When the pressurized air is shut off, nofurther atomization of the liquid occurs. Then the patient only breathesambient air which enters through the ambient air inlet at the top of thenebulizer.

It is well understood that each breath of a patient varies in volume andinspiratory flow rate. The nebulizer has an ambient air entrance at thetop to accommodate the patient's requirement for air. In operation whena patient inhales with great force, he could inhale all the atomizedaerosol in the nebulizer. There traditionally exists an unregulateddirect flow of air from the ambient entrance into the patient throughthe ambient entrance.

However, during weak inspiratory efforts the patient may inhale theatomized aerosol slowly or alternatively, after a strong inspiratoryeffort the aerosol may enter the respiratory tract at a higher flowrate. Slow inhalation of the aerosol is generally desired in order toallow the aerosolized drug to penetrate deeper into the respiratorytree.

Patients using the above system cannot self-regulate their owninspiratory flow rates. Therefore, wide ranges of inspiratory flow ratesfor each breath are to be expected. This can create an inconsistentadministration of aerosol to the respiratory tree.

Thus, it is desirable to provide a constant output flow rate of atomizeddrugs regardless of variations in inhalation pressures. The presentinvention greatly enhances the reproducibility and constancy of theoutput flow rate of atomized aerosol from a nebulizer by introducing avariable diameter input valve in the ambient entrance. The diameter ofthe valve reduces increased suction pressure caused by inhalation.

In operation the variable diameter input valve reduces its orifice sizeby means of collapsing flexible walls. The pressure inside the nebulizerdrops in proportion to the patient's inhalation force. The valve'sflexible walls collapse in proportion to the pressure differentialbetween ambient and nebulizer chamber pressures. Thus, during stronginspiratory efforts the valve's flexible walls collapse. A smaller inputorifice is formed, thereby causing the flow rate of the ambient intakeair to remain constant. It is understood that the flow rate of theambient intake air is the same as the flow rate of the patient'sinhalation. This flow rate is the nebulizer's throughput flow rate. Ahigher velocity reduced volume of air through a narrow orifice is formedwhile the nebulizer's throughput flow rate remains constant. In theopposite situation the patient performs a weak inspiratory effort. Thisresults in the valve's flexible walls remaining open. A slower buthigher volume of ambient air passes through the wider orifice. Overallwithin the normal limits of human breathing variations, the nebulizer'sthroughput flow rate through the valve's flexible walls remainsconstant. The analogous situation would be for a patient to first suckvery hard through a tiny straw for three seconds and getting 1000droplets of medicine. Next the patient would suck very lightly through awide straw for three seconds and get 1000 droplets of medicine. Theresult is that the patient inhales his medication at the same rateregardless of how hard he inhales. When the valve is employed with thedosimeter the nebulizer can be configured such that the inspiratory flowrate and the time interval of inspiration is fixed. This enables theoperator to characterize the nebulizer under such conditions such thatthe output of aerosol is consistent from discharge to discharge. Whenthe nebulizer is calibrated by weighing before and after discharge theexact amount of aerosol administered is determined. Selected amounts ofaerosolized drug may then be given by adjusting the concentration ofdrug in the nebulizer accordingly.

SUMMARY OF THE INVENTION

The main object of the present invention is to economically provide aninput regulator valve to a mixing chamber wherein variable pressureoutputs do not affect the output flow rate. This enables consistent lowinspiratory rates from a nebulizer which favors deeper penetration intothe respiratory tree for drug administration of bronchodilators,anti-inflammatory drugs, and such other drugs as may be delivereddirectly to the lung by aerosolization.

Another object of the present invention is to provide an input regulatorvalve to a mixing chamber wherein variable pressure outputs generated byapplying a vacuum to the mixing chamber do not affect (or effect in apredetermined rate of change) the output flow rate.

Another object of the present invention is to improve a nebulizer toadminister constant output rates of medication regardless of inhalationpressure.

Another object of the present invention is to utilize an input regulatorvalve in an aerosol dispenser to administer constant output rate ofmedication regardless of inhalation pressure.

Other objects of this invention will appear from the followingdescription and appended claims, reference being had to the accompanyingdrawings forming a part of this specification wherein like referencecharacters designate corresponding parts in the several views.

The present invention operates using a pressure differential and theVenturi effect (to a small extent). The Venturi effect simply stated isthe faster the flow rate, the slower the pressure inside a pipe. Theslower the flow rate, the higher the pressure inside a pipe.

The present invention uses a flexible pipe as a regulating valve. Whenthe flow rate through the regulating valve is low, the pressuredifferential between the inside of the regulating valve (the nebulizerchamber) and the outside of the outside of the regulating valve (ambientpressure) is minimal. Thus, the flexible walls of the regulating valveremain open.

However, when the patient inhales strongly the pressure differentialbetween the inside of the regulating valve and the outside of theregulating valve is maximal. Thus, the flexible walls of the regulatingvalve collapse inwards, thereby restricting the flow rate to thepatient.

One attractive use for the present invention is in respiratory therapy.A nebulizer generally is constructed as an atomizing chamber having afluid reservoir on the bottom, a pressurized air input at the bottom toatomize the fluid, a patient output tube at the top, and an ambient airentrance tube also at the top.

In operation, small amounts of pressurized air are input in half secondbursts at the bottom of the nebulizer. This atomizes the liquid antigenin the reservoir, thereby forming an aerosol in the nebulizer chamber.The patient inhales from the patient output tube. Exhalations are madeaway from the nebulizer. The patient's inhalation pressure draws amixture of aerosol and ambient air into the patient's lungs. The presentinvention inserts a flow regulating valve in the ambient air entrancetube.

During heavy inhalation, a pressure differential and the Venturi effectcauses the flexible walls of the flow regulating valve to collapse.Thus, the patient cannot increase the flow rate of his inhalationregardless of how hard he breathes. During light inhalations, thepressure differential and the Venturi effect become negligible. Theresilient, flexible walls of the flow regulating valve remain open.Thus, the patient draws his breath at the same rate as if he breathedhard.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1(a) is a side plan view of a nebulizer having a partial cutawayshowing the flexible valve.

FIG. 1(b) is a close up front plan view of the nebulizer of FIG. 1(a).

FIG. 2 is a longitudinal cross sectional view of the flexible valvetaken along line 2--2 in FIG. 1.

FIGS. 3(a), 3(b), 3(c) are front plan views looking into the tapered endof the flexible valve form inside the nebulizer during weak, medium, andstrong inhalations, respectively.

FIG. 4 is a diagram of the flexible valve with dashed lines representingthe equilibrium position, and the solid lines representing thecompressed position.

FIG. 5 is a diagram of the restoring pressure P_(R) acting on theflexible valve.

FIGS. 6(a) and 6(b) are diagrams of the flexible valve showing flowdirection and the nozzle area.

FIGS. 7(a) and 7(b) are charts showing the relationship area A topressure drop.

FIG. 8 is a chart showing the relationship of flow rate to pressuredrop.

FIG. 9 is a sectional view of the flexible valve in a portable metereddose inhaler.

Before explaining the disclosed embodiment of the present invention indetail, it is to be understood that the invention is not limited in itsapplication to the details of the particular arrangement shown, sincethe invention is capable of other embodiments. Also, the terminologyused herein is for the purpose of description and not of limitation.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring first to FIG. 1(a), a nebulizer 99 has a bowl portion 7 whichis normally filled with a liquid antigen 9. Pressurized air is fed intotube 11 at entrance 1 via known means of a pressurized tank usually setat 30 p.s.i., and a dosimeter 902 to pulse the air input and preventexcess atomization. See U.S. Pat. No. 4,106,503 (1978) to Rosenthal etal. incorporated herein by reference for a detailed disclosure. Theatomizing chamber 88 becomes filled with atomized antigen 5 as the airpasses through the liquid antigen 9 in a known manner.

The dosimeter 902 has a pressure sensor 910 which senses the onset of aninhalation. An electronic controller has a duration selector 913 forselecting the length of the air pulse to be delivered to the nebulizer99 via tube 11. A time delay selector 913 allows the operator to timethe pulse with the maximal expansion of the lungs. This maximizes theaerosol penetration into the respiratory tree.

The extension 915 has a one way valve 916. This allows the simultaneoushook-up of the dosimeter 902 to the nebulizer 99. Extension 915 providesvacuum sensing input to the dosimeter 902. This vacuum is caused by thepatient's inhalation.

In FIG. 1(b) the liquid antigen 9 is in the bowl portion 7 of the bottomhalf 950 of the nebulizer 99. The tube 11 is connected to an inlet port904 which ends in an outlet jet 905. Air is blasted against the baffle907. A straw 906 is immersed in the liquid antigen 9. As the air passesby the outlet 910 of straw 906, the Venturi effect causes a pressuredrop. This pressure drop causes liquid antigen 9 to be drawn up thestraw 906, into the air stream, and against the baffle 907. Theatomization of the liquid antigen 9 occurs in this known manner.

It has been known in the prior art that alignment of the baffle 907pointing toward the patient's output tube 17 in direction P improves theconsistency of the atomization, and consequently improves therepeatability of administering precise quantities of aerosol with eachbreath. This alignment technique used in combination with flexible valve1000 permits maximal control of administered aerosol.

The patient 4 inhales through tube 17 in direction 3 thereby inhalingthe atomized antigen 5 into his respiratory system. Concurrently duringinhalation, the flexible valve 1000 allows a certain amount of ambientair to enter the atomizing chamber 88 via inlet 2 of tube 18.

Referring next to FIG. 2, ambient air flows through inlet 2 of tube 18due to the inhalation pressure drop at P₂ which is caused by thepatient's inhalation. Ambient air flows into the atomizing chamber 88between valve lips 152,153. P₂ is now lower than P₁. This causes forcevectors V₁, V₂ to close valve lips 152, 153. The Venturi effect alsoadds to vectors V1, V2. Thus, P₂ drops due to the patient's inhalationand the Venturi effect.

The lips 152, 153 are flexible. They are preferably made of any flexibleresilient material such as rubber, plastic, silicon, neoprene, nitrate,fluorocarbon, vinyl, propylene, butyl, or other compounds. The flexiblevalve 1000 is constructed to maintain a fixed diameter d₁, at flex point100 during all flow conditions. Only the lips 152, 153 are flexibleunder pressure drops between P₁ and P₂ . Mounting supports 150, 151secure the flexible valve 1000 inside tube 18.

Referring next to FIG. 3(a), the patient is inhaling very weakly. Thus,the orifice 300 between lips 152, 153 have been forced together forminga smaller orifice 400. Thus, the output flow has remained constant dueto the higher speed air through the smaller orifice 400.

Finally, in FIG. 3(c), the patient has drawn a strong breath. Thepressure drop of P₂ has practically closed off orifice 500. The outputflow rate remains constant. In all instances the ambient air input intothe nebulizer is the same as the nebulizer output pulled in by thepatient

The exact distortion of lips 152, 153 depends on numerous variablesincluding inhalation flow rate, fluid density, and ambient pressuredifferentials between P₁ and P₂. Variable flow compensations can beachieved by various types of lips 152, 153, the length to width ratio ofthe orifice 300, the wall angles and length, as well as the materialproperties. The nebulizer's output flow rate and orifice closure can becontrolled in any desired way for various pressure differences, notnecessarily to a constant value. It is, therefore, possible to designthe lips 152, 153 in such a manner as to create a customizedrelationship between the nebulizer's throughput and the patient'sinhalation pressure.

EXAMPLE

The effects of regulating the inspiratory flow rate (0.25 L/sec) with anewly created valve and fixation of the nebulizer straw and baffleposition were studied as means of enhancing the output reproducibilityof the DeVilbis 646 nebulizer when used with a Dosimeter.

Twelve patients took 10 breath actuated inhalations of saline from anebulizer attached to a Dosimeter set at 0.6 seconds. After disassemblyand refill, the 10 breath sequence w repeated 4 more times. All patientsconducted this procedure with nebulizers configured as follows: A:Random or varied position of straw and baffle without valve in place; B:Position of straw and baffle fixed without valve in place; C: Straw andbaffle fixed with valve in place. The average weights of aerosol (mg)delivered was as follows: A: 0.09634+/-0.002847, B: 0.08057+/-0.002128,C: 0.06691+/-0.000859. All group means were significantly different fromone another (p=0.01).

Fixation of the straw and baffle position increased the reproducibilityof nebulizer output between nebulizer refills with considerable furtherenhancement by the addition of a special valve that regulated theinspiratory flow rate. These measures enable the calibration of theDeVilbis 646 nebulizer when a Dosimeter is used, thereby enablingdelivery of specific target quantities of aerosol at a known inspiratoryflow rate.

Referring last to FIG. 9 a drug delivery system (DDS) 500 is shown insectional view. DDS 500 is a portable, pocket size device used todispense and inspire medications from a conventional metered doseinhaler (MDI) 501. The primary design features of the DDS 500 are:

Flow rate control of the mixture of inspiratory and medication.

Gravitational and aerodynamic separation of the atomized medication byparticle size.

The physical components of the DDS 500 are designated with numbers. Themedication, propellants, and air that are not permanent parts of the DDS500 are designated with letters. A tube body 503 is cylindrical inshape. It houses a conventional MDI 501, a seal retainer 504, adischarge tube seal 505, and a discharge seat 506. The tube body 502telescopes into the medication separation chamber 507 when not in use.Retainer strap 512 holds the MDI 501 in place.

The MDI 501 can be any number of commercially available atomizingmedication dispensers using liquid propellants (preferablyfluorocarbons) in a canister. Seal retainer 504 releasably holds thetube body 502 to the medication separation chamber 507. The dischargetube seal 505 is a soft o-ring seal (preferably made of silicon orbutyl). It holds and releasably seals the discharge tube 514.

The discharge seat 506 is a notch that restrains the movement of thedischarge tube 514 thereby enabling the activation of the MDI 501. Themedication separation chamber 507 receives the MDI 501 discharge blastsA. It also houses the tube body 502 when not in use.

The flow control valve 508 is identical to that described as the valvebody 1000 of FIGS. 1-8. The large particle well 509 is the bottomportion of the medication separation chamber 507. The large medicationparticles B2 precipitate therein. Large medication particles B2 therebykeep clear of the inlet air stream D.

The medication chamber exit 510 is an orifice for the mixture of smallmedication particles B1 and air to exit to the mouthpiece 511. Themouthpiece 511 is a tube from the medication separation chamber 507 tothe patient for inspiration of the aerosol medication. The telescopingstop 513 is a circumferential ring that stops the tube body 502 fromover-inserting into the medication separation chamber 507. It may alsobe used as a grip for retraction of tube body 502 to the operationalposition shown in FIG. 9.

The tube body 502 can be made of molded plastic. The seal/retainer 504,discharge tube seal 505, and flow control valve 508 can be made from thegroup consisting of rubber, vinyl, plastic, silicon, fluorosilicon,fluorocarbon, nitrile, butyl, or nylon.

In operation the tube body houses members 501, 504, 505 and 506 in theircorrect working relative positions. The MDI 501 is discharged in thenormal way, i.e., by depressing the MDI 501 relative to the dischargetube 514 until the contents of the MDI 501 are released. The meteredcharge A contains medication, a medication vehicle (usually a fattyacid), and propellants (usually a combination of fluorocarbons). Thetube body 502 and the medication separation chamber 507 seal/retainer504 holds the tube body in their correct operating positions andprovides a seal. The discharge tube seal 505 is an o-ring type of sealthat does not allow air to enter the chamber during use. The dischargeseat 506 is simply a stop that restricts movement of the MDI dischargetube 54 so that the MDI 501 can be pushed into the medication separationchamber 507. This component is common to most MDI dispensers, and is nota significant aspect of this device.

Upon activation of the MDI 501 its discharge A enters the multi-functionmedication separation chamber 507. This chamber performs the followingfunctions:

1. Cushion the MDI discharge blast A and hold the aerosol medication B1,B2 statically for comfortable patient inhalation not requiringcoordination with the MDI activation.

2. Separates the small desirable aerosol medication droplets, B1, fromthe larger undesirable droplets, B2. The design features that allowthese functions to be performed are described below:

(1) MDI Discharge Cushion

The MDI discharge is strong enough to be Undesirable because it isuncomfortable for patients and, due to its high momentum, deposits muchof the aerosol medication on the patient's throat and mouth. Themedication separation chamber 507 acts as a damper and cushion for thedischarged propellant and medication. The very high vapor pressures ofthe most common fluorocarbon propellants force these propellants tovaporize very rapidly when exposed to ambient conditions. When the MDIcharge chamber valve is open, the vapor pressure forces the liquidpropellant, vehicle, and medication mixture out of the MDI withconsiderable velocity. Immediately after jettison, the propellant veryrapidly vaporizes breaking the vehicle/medication droplets into smallerand smaller pieces, B1, B2. However, there is still momentum of themixture away from MDI. The medication separation chamber, 507, has anearly closed volume, and, thus, slows the momentum of the MDI dischargeby the increasing back pressure at the closed end of the chamber. At theend of this process the atomized vehicle/medication droplets B1 arenearly static in the chamber for patient inspiration without theproblems of MDI blast and the normally required MDI activation andinhalation coordination.

(2) Separation of Aerosol Droplets by Size

Current literature on MDI efficiency indicates that, of the widedistribution of atomized medication vehicle droplet sizes produced bymost MDIs, only droplets of 8 microns or less are inspired deep into thepatient's lungs. Larger droplets are too massive to make the turns ofthe throat and bronchial tree without being centrifugally thrown ontothe walls of the respiratory track. Here they are absorbed into thepatient's bloodstream which enhancing respiratory function. Themedication separation chamber 507 allows the larger droplets to settleto the bottom of the chamber in three different ways to insure that theyare not part of the air-medication mixture E inspired by the user.First, at the time of MDI discharge, the largest droplets directlyimpact the bottom of the chamber even though a blast dampening, asdiscussed earlier, is provided. Second, the large particles have asettling rate of one cm/s or more (10 times greater than particles ofthe optimum size) and simply fall on and adhere to the bottom of thechamber before the patient inspiratory effort begins. Finally, thelarger droplets continue to fall during inspiration, because their rateof descent is approximately that of the inspired air's D flow ratethrough the chamber. The flow rate is relatively low because of the flowrate limit imposed by the flow control valve 508.

The flow control valve 508 is a flexible valve that limits the inlet airflow to a desired maximum, independent of patient maximum effort.Minimum flow rate is obviously user controlled. The design of the flowcontrol valve is provided in the description of FIGS. 1-9. Only theintegral function of this valve in this device is discussed here. Thevalve is designed and fabricated to limit the maximum inspiratory flowrate to the patient primarily for optimum distribution of the aerosol inthe lung. This flow rate is 0.5 liters per second for adult users. It iswell documented in the current literature. The valve and the resultingmaximum flow rate may be easily changed to suit individual patientneeds, to take best advantage of current MDI performance, or to bestreflect current medical belief. The remaining three components are selfexplanatory from FIG. 9. The air inlet 900 is simply a perforated endcap to the but 199 that allows free entry of air and protects the flowcontrol valve 508. The medication chamber exit 510 can be sized formaximum patient benefit. It must be kept larger than the maximum orificeof the flow control valve 508. The mouthpiece 11 may be used as a capfor the tube body on the MDI end or may be made to fold onto the tubebody.

Although the present invention has been described with reference topreferred embodiments, numerous modifications and variations can be madeand still the result will come within the scope of the invention. Nolimitations with respect to the specific embodiments a disclosed hereinis intended or should be inferred.

MATHEMATICAL DISCUSSION

Valve Element Restoring Force

If the valve body 1000 in FIG. 4 is deformed then there is a "restoring"force F_(R) that acts to restore the valve to the original shape. InFIG. 4, the dashed lines represent the equilibrium position of thevalve, solid lines represent the compressed position.

The restoring force F_(R) is proportional to and acts in a directionopposite that of the deflection x.

    F.sub.R =k.sub.1 x

The valve of the proportionality constant K₁ depends on the geometricand material parameters of the valve. F_(R) is shown above acting on asingle pair of points of the valve. However, it would be distributedalong the surface as shown in FIG. 5. In general, when a force isdistributed over a surface it is referred to as a pressure. Therestoring P_(R) can be variable over the surface. The exact shape of thedistribution depends on the geometric and material parameters of thevalue 1000.

Pressure Driven Flow

A situation is now analyzed where a pressure drop is imposed across thevalve. If a pressure drop is imposed across the valve P₂ >P₁ then a flowQ will result. This is shown in FIG. 6(a).

The force balances on the valve surface is shown in FIG. 6 (b). Theforces acting on the valve surface must be in equilibrium (because thevalve is not in motion). Acting on the inner surface is the pressure P₂.Acting on the outer surface is pressure P₁. An additional pressure termis required to balance the differences between P₂ and P₁. This pressureterm is the restoring pressure PR (noted above) that accompanies adeformation of the valve. The valve nozzle N (defined as the point ofminimum cross section area) will, therefore, decrease in size if P₂ <P₁.There will be a slight variation in pressure along the cross section dueto the Bernoulli effect (Venturi effect). This variation is slight. Thenew force balance is shown in FIG. 6(b).

Flow Equation

The valve nozzle area A varies depending on pressure drop ΔP=P₁ -P₂.This relationship is shown in FIG. 7(a), 7(b). The shape of the line (orcurve) C will depend on the geometric and material parameters of thevalve. The important thing to note is that the area A increases withdecreasing values of ΔP, and vice versa. The relationship can beexpressed mathematically as:

    A=A.sub.0 -K.sub.2 ΔP

The term A₀ is the area corresponding to ΔP=0. The flow rate Q throughthe nozzle area A of FIG. 7(a) will depend on the area A and thepressure drop ΔP=P₁ -P₂ : ##EQU1## The flow rate Q is therefore:##EQU2## The valves of the proportionality constants K₂ and K₃, dependon the geometric and material properties of the valve. The equationabove is plotted in FIG. 8.

While the shape of the curve will depend on the geometric and materialproperties of the valve, there are two important things to note:

1. In the nebulizer application shown in FIGS. 1-3 the following is adescription of FIG. 8:

Starting with ΔP=0 the flow rate Q initially increases with increasingvalues of ΔP. Increasing ΔP beyond ΔP₁, is accompanied by a decrease inthe flow rate Q. At a high enough value of ΔP(ΔP₂) the flow rate will bezero.

2. For other applications ΔP<0 (P₂ >P₁):

Starts with ΔP=0 the flow rate in the opposite direction of Q willincrease "rapidly" with increasing values of ΔP. This rate of change ismuch larger than observed with the area because of the ΔP term is theflow equation.

The valve must be configured such that P1 is atmospheric and P2 is thepressure within the nebulizer chamber. When the patient breathes theobserved condition is P₂,P₁ (ΔP,0). If the magnitude of ΔP exceeds ΔP₁,then the amount of air entering the nebulizer through the valvedecreases.

It is understood that the placement of the above described valve in anebulizer could be either in the inlet or the outlet portion thereof. Itis further understood that the above described valve also functions as asafety valve for pressure release should an accidental pressurizationoccur in the nebulizer.

Although the present invention has been described with reference topreferred embodiments, numerous modifications and variations can be madeand still the result will come within the scope of the invention. Nolimitation with respect to the specific embodiments disclosed herein isintended or should be inferred.

I claim:
 1. A portable drug delivery system comprising:a tube body; amedication separation chamber; a connection between the tube body andthe medication separation chamber; said tube body further comprising apressurized metered dose inhaler for injecting a metered blast ofmedication from the pressurized metered dose inhaler into the medicationseparation chamber; said medication separation chamber furthercomprising a patient inhalation mouthpiece having an exit orifice fromthe medication separation chamber; a patient initiated variable vacuumon the mouthpiece creating an output flow; and said medicationseparation chamber further comprising an air inlet orifice having aflexible valve with a variable cross-sectional orifice resulting in aconstant output flow rate of the metered blast of medication regardlessof the patient initiated variable vacuum other than for a zero vacuum.2. The drug delivery system of claim 1, wherein said medicationseparation chamber further comprises a bottom portion for collectinglarge drops of the metered blast of medication.
 3. The drug deliverysystem of claim 1, wherein said flexible valve further comprises aflexible nozzle having a set of flexible lips angled toward one anotherforming the cross-sectional orifice facing upstream of airflow, saidpatient initiated vacuum reducing a cross-sectional area of the orificeby collapsing the flexible lips in proportion to the increased vacuum.4. A portable drug delivery system comprising:a tube body connected to amedication separation chamber; a union between the tube body and saidmedication separation chamber; said tube body further comprising apressurized metered dose inhaler having an injector for injecting ametered blast of medication from the pressurized metered dose inhalerinto the medication separation chamber; said medication separationchamber further comprising a patient inhalation mouthpiece having anexit orifice from the medication separation chamber; said medicationseparation chamber further comprising an air inlet orifice having aflexible valve; a patient initiated variable vacuum on the mouthpiececreating an output flow from the medication chamber; said flexible valvehaving a nozzle which varies in its cross-sectional area; and saidnozzle having flexible walls forming an orifice and having an exposureupstream to ambient pressure and exposure downstream to a medicationseparation chamber pressure, wherein said patient initiated variablevacuum reduces a cross-sectional area of the orifice by collapsing theflexible walls in proportion to an increased vacuum, resulting in aconstant output flow rate of the medication regardless of the patientinitiated variable vacuum other than for a zero vacuum.
 5. The drugdeliver system of claim 4, wherein said medication separation chamberfurther comprises a bottom portion for collecting large drops of themetered blast of medication.
 6. The drug delivery system of claim 4,wherein said flexible walls further comprise a material selected fromthe group consisting of rubber, plastic, silicon, neoprene, nitrate,fluorocarbon, vinyl, propylene, and butyl.